Posttraumatic stress disorder (PTSD) is a prevalent psychiatric disorder estimated to occur in approximately 10% of the United States population and, in a third of sufferers, the condition is chronic. Cigarette smoking is highly co-morbid with PTSD. Thirty-fifty percent of individuals with PTSD smoke cigarettes and are more likely to be heavy smokers. Our previous work has suggested that compared to non-PTSD smokers, context (particularly stress-related and trauma-related contexts) significantly impacts smoking craving and smoking topography in smokers with PTSD. Individuals with PTSD exhibit deficits in neurocognitive test performance, particularly in the areas of attention and memory, as well as sensorimotor gating as assessed by gating as assessed by prepulse inhibition (PPI) of the startle response. Our pilot data suggest that compared to smokers without PTSD, nicotine enhances the startle response in PTSD smokers and improves PPL What is needed now is to utilize objective measures such as startle and PPI paradigms to carefully investigate the effect of context and cigarette smoking in this high-risk psychiatric population. The overall purpose of this exploratory/developmental grant is to study the use of startle and PPI as measurement parameters for smoking and smoking withdrawal in smokers with PTSD. The proposed study will build on our previous findings and initial pilot data. Using a 2(group, PTSD versus non-PTSD) X 2(content, trauma versus neutral) X 3(smoking condition, usual brand vs. no nicotine vs. no smoking) design with varying PPI intervals, the study is designed to: a) examine the effects of acute smoking abstinence and smoking on PPI in smokers with PTSD compared to smokers without PTSD but with trauma exposure; b) evaluate the contextual effect of trauma versus neutral script presentations; c) examine the parameters of prepulse intervals on PPI over these experimental manipulations; and d) investigate possible attentional mechanisms of smoking by administering neurocognitive measures across nicotine conditions. This ultimate goal of this line of research is to inform the development of smoking cessation strategies in PTSD smokers by identifying mechanisms of smoking that may be present in smokers with PTSD. [unreadable] [unreadable]